Author | dc.contributor.author | Abin Carriquiry, Juan Andrés | |
Author | dc.contributor.author | Voutilainen, Merja H. | es_CL |
Author | dc.contributor.author | Barik, Jacques | es_CL |
Author | dc.contributor.author | Cassels Niven, Bruce | es_CL |
Author | dc.contributor.author | Iturriaga-Vásquez, Patricio | es_CL |
Author | dc.contributor.author | Bermúdez, Isabel | es_CL |
Author | dc.contributor.author | Durand, Claudia | es_CL |
Author | dc.contributor.author | Dajas, Federico | es_CL |
Author | dc.contributor.author | Wonnacott, Susan | es_CL |
Admission date | dc.date.accessioned | 2008-12-03T15:22:57Z | |
Available date | dc.date.available | 2008-12-03T15:22:57Z | |
Publication date | dc.date.issued | 2006 | |
Cita de ítem | dc.identifier.citation | EUROPEAN JOURNAL OF PHARMACOLOGY Volume: 536 Issue: 1-2 Pages: 1-11 Published: APR 24 2006 | en |
Identifier | dc.identifier.issn | 0014-2999 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/118748 | |
Abstract | dc.description.abstract | Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory roles in the brain, making them attractive therapeutic targets. Natural products provide key leads in the quest for nicotinic receptor subtype-selective compounds. Cytisine, found in Leguminosae spp., binds with high affinity to alpha 4 beta 2* nicotinic receptors. We have compared the effect of C3 and C5 halogenation of cytisine and methylcytisine (MCy) on their interaction with native rat nicotinic receptors. 3-Bromocytisine (3-BrCy) and 3-iodocytisine (3-ICy) exhibited increased binding affinity (especially at alpha 7 nicotinic receptors; K-1 similar to 0.1 mu M) and functional potency, whereas C5-halogenation was detrimental. 3-BrCy and 3-ICy were more potent than cytisine at evoking [H-3]dopamine release from striatal slices (EC50 similar to 11 nM), [H-3]noradrenaline release from hippocampal slices (EC50 similar to 250 nM), increases in intracellular Ca2+ in PC12 cells and inward currents in Xenopus oocytes expressing human alpha 3 beta 4 4 nicotinic receptor (EC50 similar to 2 mu M). These compounds were also more efficacious than cytisine. C3-halogenation of cytisine is proposed to stabilize the open conformation of the nicotinic receptor but does not enhance subtype selectivity. | en |
Lenguage | dc.language.iso | en | en |
Publisher | dc.publisher | ELSEVIER | en |
Keywords | dc.subject | H-3 DOPAMINE RELEASE | en |
Título | dc.title | C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists | en |
Document type | dc.type | Artículo de revista | |